The microbiome begins at birthi and establishes itself during the neonatal period. There is a growing appreciation ofthe microbiome's critical role in human health. Thus, any perturbations in microbial acquisition early in life might be expected to influence disease risk. Yet, the relationship between microbiome development in infants, the developing immune system and infection risk has just begun to be explored epidemiologically. The overarching goal ofthis project is to fill this critical research gap by examining the role of the developing infant intestinal microbiota, maternal/fetal risk factors, neonatal exposures and diet in relation to the risk of infant infection and allergy/atopy using newly advanced sequencing techniques to capture the microbiome. The proposed research will leverage the ongoing New Hampshire Birth Cohort Study, enabling evaluation of the microbiome in repeated measures of 250 infants over the first year of life, beginning with fetal life, and with subsequent follow-up for infant outcomes up to 3 years of age in collaboration with Project 3. We will utilize culture-independent, massively parallel sequencing methods that will allow complete identification of microbial populations associated with health and disease. Thus, our proposed comprehensive longitudinal assessment ofthe microbiota will be conducted in a large cohort of infants beginning at birth, on whom epidemiologic data on maternal and infant diet and other exposures, as well as episodes of infection and allergy/atopy, are being collected. Specifically, we will test the following hypotheses: 1) perinatal and neonatal gut microbial colonization is associated with risk of infection and allergy/atopy and 2) prenatal and neonatal factors, including maternal obesity, maternal infection, breast feeding and vitamin D exposure is associated with altered microbial acquisition and altered disease risk. Our research will significantly advance our knowledge regarding the relationship between the developing microbiome, environmental exposures in fetal and neonatal life, and risk of infection and allergy/atopy, and lead to new paradigm for assessing and preventing common disorders of childhood and adult life.